The present invention relates to a method for separation of optical isomers. More particularly, the present invention relates to an efficient method for optical resolution of optical isomers using simulated moving bed chromatographic apparatus.
As an industrial method for isolating an object component from an isomer mixture stock solution containing more than one isomers, chromatography is widely employed.
Chromatography is a method of separation comprising using an adsorption column packed with an adsorbent such as ion exchange resin, zeolite, silica gel and the like as a filler and separating components by making use of the difference in their adsorbabilities by the adsorbent. In this method, water, an organic solvent or a mixture thereof is used as an eluent. A high purity object component can be obtained by concentrating the eluent portion containing the object component.
There are known batch system chromatography and simulated moving bed chromatography.
Especially, simulated moving bed chromatography is very hopeful as a method for commercial scale separation of isomers for the reasons that the required amount of the eluent is smaller than required in the batch system chromatography, continuous separation of components is possible, etc.
In simulated moving bed chromatography, however, an expensive support such as silica gel must be used for the filler. The fact that there is no inexpensive effective filler provided with excellent optical resolution ability has been an obstacle to the positive employment of simulated moving bed chromatography, the apparatus for which is also relatively expensive per se.
Therefore, an adsorbent, which does not require expensive silica gel as a support, is inexpensive per se and has excellent ability of separating optically active isomers, has been desired.
This invention is made under the above-described circumstances. That is, the object of this invention is to provide a method for separation of optical isomers which is able to efficiently effect optical resolution of an optical isomer mixture using a filler for optical resolution, which is inexpensive per se, has excellent ability of optical resolution and requires no expensive silica gel support.
We intensively coped with the problem and found, in the separation method using the simulated moving bed chromatographic apparatus, that optical isomer mixtures can be efficiently separated by using particles of a polysaccharide derivative as a filler for optical resolution without using expensive silica gel and completed the present invention.
A first embodiment of this invention is, in the method of separation of optical isomers, which comprises using a simulated moving bed chromatographic apparatus comprised of a plurality of columns packed with an optical resolution filler and endlessly connected and a circulating pump which circulates a fluid in one direction through the plurality of the columns, wherein an optical isomer mixture solution and an eluent are introduced into said fluid flow and simultaneously a solution rich in non-adsorbable or poorly-adsorbable substances and a solution rich in adsorbable or strongly adsorbable substances are simultaneously taken out, an inlet for a fluid to be introduced into the columns and an outlet for a fluid to be taken out of the columns are alternately arranged in the direction of the circulating fluid and said inlet and outlet are intermittently shifted in the direction of the fluid flow, a method characterized in that particles of a polysaccharide derivative are used as said filler for optical resolution.
A second embodiment of the invention is a method of separation of optical isomers of the first embodiment in which an ester derivative and/or a carbamate derivative of the polysaccharide is used.
A third embodiment of this invention is a method of separation of optical isomers of the first embodiment in which the polysaccharide derivative is that in which all or a part of hydrogen atoms of the hydroxyl or amino groups of the polysaccharide are substituted with at least one of the atom groups represented by the following formula (1), (2), (3) or (4): 
wherein R is an aromatic group which may contain a hetero atom and may be unsubstituted or substituted with at least one group or atom selected from a class consisting of C1-12 alkyl group, C1-12 alkoxyl group, C1-12 alkylthio group, cyano group, halogen atom, C1-8 acyl group, C1-8 acyloxy group, hydroxyl group, C1-12 alkoxycarbonyl group, nitro group, amino group and C1-8 dialkylamino group; and X is a C1-4 hydrocarbyl group which may contain a double bond or a triple bond.
A fourth embodiment of this invention is a method of separation of optical isomers of said first or second embodiment, in which the polysaccharide derivative is a carbamate derivative of polysaccharide which is obtained by reacting an isocyanate represented by the following formula (5) or (6) with the polysaccharide or an ester derivative of polysaccharide which is obtained by reacting an acid chloride represented by the following formula (7) or (8) with the polysaccharide: 
wherein R is an aromatic group which may contain a hetero atom and may be unsubstituted or substituted with at least one group or atom selected from a class consisting of C1-12 alkyl group, C1-12 alkoxyl group, C1-12 alkylthio group, cyano group, halogen atom, C1-8 acyl group, C1-8 acyloxy group, hydroxyl group, C1-12 alkoxycarbonyl group, nitro group, amino group and C1-8 dialkylamino group; and X is a C1-4 hydrocarbyl group which may contain a double bond or a triple bond.
A fifth embodiment of this invention is a method of separation of optical isomers of any of said first to fourth embodiments in which the polysaccharide is cellulose.
A sixth embodiment of this invention is a method of separation of optical isomers of any of said first to fifth embodiments, in which the number average degree of polymerization is not less than 5.
A seventh embodiment of this invention is a method of separation of optical isomers of any of said first to sixth embodiments, in which the number average degree of polymerization is 10-2,000.
An eighth embodiment of this invention is a method of separation of optical isomers of any of said first to seventh embodiments, in which the degree of introduction of the substituents in the polysaccharide is 10-100%.
A ninth embodiment of this invention is a method of separation of optical isomers of any of said first to seventh embodiments, in which the degree of introduction of the substituents in the polysaccharide is 30-100%.
A tenth embodiment of this invention is a method of separation of optical isomers of any of said first to ninth embodiments, in which said derivative of the saccharide is in the form of particles having a particle diameter of 10-300 xcexcm, a specific surface area of 0.5-300 m2/g.